Serum from 44 volunteers and 21 patients with acute hepatitis and 18 with cirrhosis were tested for the total and unsaturated folate binding capacity (TFBC-UFBC). A high level of TFBC was noted in acute hepatitis (p < 0.001) and in cirrhosis (p < 0.05), whereas only in the last case a reduced UFBC was present (p < 0.05). When serum from patients with acute hepatitis was eluted on Sephadex G-200 after incubation with radioactive folic acid (500 pg), two main peaks were observed, one in the exclusion peak of protein and the second in the position of the only binder found in normal serum (MW 43,000). A third small peak was also present in the position corresponding to a MW of 20,000. These findings documented the release of binders from hepatic cell when a massive necrosis of liver occurs.